JP2017500337A - Oral care composition comprising serine and at least one zinc salt - Google Patents

Abstract

An oral care composition comprising serine and one or more zinc salts for use in reducing or inhibiting biofilm formation in the oral cavity.

Description

  Plaque is a biofilm that adheres to teeth and other oral surfaces, particularly to the gingival margin, and is associated with the occurrence of gingivitis, periodontitis, caries, and other periodontal diseases. Plaque is sticky and has a strong resistance to removal from the teeth and / or oral surface. Plaque contains glucan. Glucan is an insoluble polysaccharide that imparts its sticky properties to plaque. Glucosyltransferase, a bacterial enzyme, converts edible sugars to glucans. Plaques calcify to form hard deposits called calculus (or calculus), which are locally irritating to the gums, causing gingivitis.

  Various antibacterial agents can retard bacterial growth, thereby reducing oral surface biofilm formation.

  Zinc and other metal compounds / salts have long been used as antimicrobial agents. Without being bound by any theory, free zinc ions are believed to confer antibacterial efficacy by inhibiting glucose metabolism and / or interacting with the bacterial cell wall and reducing bacterial colonization in the oral cavity. (As described in Cummins D., J Clin Periodonol 1991, 18, 455-461). Zinc oxide, an insoluble zinc compound, may also be able to provide strong antimicrobial efficacy during tooth brushing.

  It would be desirable to provide an oral care composition that exhibits a biofilm reduction efficacy that is even greater than known compositions.

  An oral care composition is provided comprising (a) serine and (b) zinc oxide and zinc citrate in a zinc oxide to zinc citrate weight ratio of 1.5: 1 to 4.5: 1.

  Optionally, the composition is oxidized from 1.5: 1 to 4: 1, 1.7: 1 to 2.3: 1, 1.9: 1 to 2.1: 1, or about 2: 1. It has a weight ratio of zinc to zinc citrate. Corresponding molar ratios based on these weight ratios can also be used.

  Optionally, the composition comprises serine in an amount of 0.05 wt% to 0.8 wt%, or 0.075 wt% to 0.25 wt%, based on the total weight of the composition. Further optionally, the composition comprises serine in an amount of 0.12% to 0.25% by weight, based on the total weight of the composition. Further optionally, the composition comprises serine in an amount of 0.14% to 0.20% by weight, based on the total weight of the composition. Still further optionally, the composition comprises serine in an amount of about 0.15% by weight, based on the total weight of the composition.

  Optionally, the composition comprises zinc oxide in an amount of 0.5 wt% to 1.5 wt%, and citric acid in an amount of 0.25 wt% to 0.75 wt%, based on the total weight of the composition. Contains zinc. Further optionally, the composition comprises zinc oxide in an amount of about 1% by weight, and zinc citrate in an amount of about 0.5% by weight, based on the total weight of the composition.

  Also provided are oral care compositions comprising (a) serine and (b) one or more zinc salts for use in reducing or inhibiting biofilm formation in the oral cavity.

  Optionally, serine is present in the composition in an amount of 0.05% to 0.8% by weight, based on the total weight of the composition. Further optionally, the serine is present in the composition in an amount of 0.05% to 0.39% by weight, based on the total weight of the composition. Still further optionally, the composition comprises serine in an amount of 0.075% to 0.25% by weight, based on the total weight of the composition. Still further optionally, the composition comprises serine in an amount of 0.12% to 0.25% by weight, based on the total weight of the composition. Further optionally, the composition comprises serine in an amount of 0.14% to 0.20% by weight, based on the total weight of the composition. Still further optionally, the composition comprises serine in an amount of about 0.15% by weight, based on the total weight of the composition.

  Optionally, the molar ratio of serine: total zinc salt is 0.01: 1 to 3: 1.

  Optionally, the total concentration of zinc salt in the composition is from 0.2 wt% to 5 wt%, based on the total weight of the composition.

  Optionally, at least one of the one or more zinc salts described above is zinc oxide.

  Optionally, at least one of the one or more zinc salts described above is zinc citrate.

  Optionally, the composition comprises zinc oxide in an amount of 0.5 wt% to 1.5 wt%, and citric acid in an amount of 0.25 wt% to 0.75 wt%, based on the total weight of the composition. Contains zinc. Further optionally, the composition comprises zinc oxide in an amount of about 1% by weight, and zinc citrate in an amount of about 0.5% by weight, based on the total weight of the composition.

  Also provided is a method of reducing or inhibiting biofilm formation in the oral cavity, the method comprising contacting the oral cavity with any oral care composition.

  Also provided is the use of a combination of (a) serine and (b) one or more zinc salts in oral care compositions for reducing or inhibiting biofilm formation in the oral cavity.

  Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.

  The following description of preferred embodiments is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.

  As used throughout, ranges are used as shorthand to describe each and every value that is within the range. Any value within the range can be selected as the upper and lower limits of the range. Further, all references cited herein are incorporated by reference in their entirety. In the event that the definition of the present disclosure and that of a cited reference conflict, the present disclosure shall control.

  Unless stated otherwise, all percentages and amounts expressed herein are to be understood as meaning percentages by weight. The given amount is based on the active weight of the material.

  The present inventors have surprisingly found that adding serine to an oral care composition containing a zinc salt improves the biofilm reduction efficacy of the oral care composition. The inventors have also discovered that there is an optimal concentration of serine that optimizes the biofilm reducing efficacy of the zinc salt-containing oral care composition, which was unexpected.

  In a first aspect, the oral care composition comprises (a) serine and (b) zinc oxide and zinc citrate in a weight ratio of zinc oxide to zinc citrate of at least 1.5: 1 to 4.5: 1. Things are provided.

  Optionally, the composition comprises 1.5: 1 to 4: 1, 1.7: 1 to 2.3: 1, 1.9: 1 to 2.1: 1, or about 2: 1 zinc oxide. Having a weight ratio of zinc citrate. Corresponding molar ratios based on their weight ratio can also be used.

  In a second aspect, an oral care composition is provided comprising (a) serine and (b) at least one zinc salt for use in reducing or inhibiting biofilm formation in the oral cavity. In some embodiments, the serine is 0.05% to 0.8%, 0.05% to 0.75%, or 0.05% to 0% based on the total weight of the composition. It may be present in the composition in an amount of .39% by weight.

  In a third aspect, there is provided a method for reducing or inhibiting biofilm formation in the oral cavity, the method comprising contacting the oral cavity with an oral care composition comprising (a) serine and (b) at least one zinc salt. including. In some embodiments, the serine is 0.05% to 0.8%, 0.05% to 0.75%, or 0.05% to 0% based on the total weight of the composition. It may be present in the composition in an amount of .39% by weight.

  In a fourth aspect, there is provided the use of a combination of (a) serine and (b) at least one zinc salt in an oral care composition for reducing or inhibiting biofilm formation in the oral cavity. In some embodiments, the serine is 0.05% to 0.8%, 0.05% to 0.75%, or 0.05% to 0%, based on the total weight of the composition. It may be present in the oral care composition in an amount of 39% by weight.

  In a fifth aspect, the oral care composition of the first aspect is provided for use in reducing or inhibiting biofilm formation in the oral cavity.

  In a sixth aspect, a method for reducing or inhibiting biofilm formation in the oral cavity is provided, the method comprising contacting the oral cavity with the oral care composition of the first aspect.

  In each of the preceding embodiments, the serine is 0.075 wt% to 0.35 wt%, 0.075 wt% to 0.30 wt%, 0.075 wt% to 0.005 wt% based on the total weight of the composition. 25 wt%, 0.12 wt% to 0.25 wt%, 0.14 wt% to 0.20 wt%, 0.14 wt% to 0.18 wt%, 0.14 wt% to 0.16 wt% %, Or about 0.15% by weight in the oral care composition.

  In any embodiment of each of the foregoing aspects, the molar ratio of serine to total zinc salt is 0.01: 1 to 3: 1, 0.01: 1 to 2.2: 1, 0.02: 1. -1.4: 1, 0.05: 1 to 0.3: 1, 0.1: 1 to 0.2: 1, or about 0.1: 1.

  Examples of suitable zinc salts that may be used in the composition of any of the previous embodiments include (but are not limited to) zinc oxide, zinc citrate, zinc lactate, zinc chloride, zinc acetate, zinc gluconate, Zinc glycine, zinc sulfate, sodium zinc citrate, and mixtures thereof are included. In any of the preceding aspects, at least one of the one or more zinc salts may be zinc oxide. Additionally or alternatively, at least one of the one or more zinc salts may be zinc citrate. In some embodiments, the total concentration of zinc salt in the composition, based on the total weight of the composition, is 0.2 wt% to 5 wt%, 0.5 wt% to 2.5 wt%, 0.8 wt% % To 2% by weight, or about 1.5% by weight.

  In any embodiment of each of the preceding aspects, the composition is zinc oxide in an amount of 0.5 wt% to 1.5 wt%, and 0.25 wt% to 0 wt%, based on the total weight of the composition. It may contain zinc citrate in an amount of .75% by weight. Alternatively, the composition comprises zinc oxide in an amount of 0.75 wt% to 1.25 wt%, and zinc citrate in an amount of 0.4 wt% to 0.6 wt%, based on the total weight of the composition. May be included. Alternatively, the composition may comprise zinc oxide in an amount of about 1% by weight and zinc citrate in an amount of about 0.5% by weight, based on the total weight of the composition.

  In any embodiment of each of the previous aspects, the composition may further comprise one or more abrasives. Suitable abrasives that can be included in the composition include, but are not limited to, silica abrasives, aluminum oxide, aluminum silicate, calcinated alumina, bentonite, other siliceous materials, insoluble phosphates Natural calcium carbonate, precipitated calcium carbonate, and mixtures thereof. In some embodiments, at least one of the one or more abrasives is a silica abrasive. Examples of silica abrasives include, but are not limited to, an average particle size of up to about 20 microns (such as Zedent 105 and Zedent 114 sold by JM Huber Chemicals Division, Haver de Grace, Md. 21078). Syrodent 783 (sold by Davison Chemical Division of WR Grace & Company) or Sorbosil AC 43 (from PQ Corporation). In some embodiments, at least one of the one or more abrasives is a calcium carbonate abrasive such as precipitated calcium carbonate (PCC) or natural calcium carbonate (NCC).

  In any embodiment of each of the preceding aspects, the composition may further comprise an anticalculus (calculus control) agent. Suitable anti-calculus agents include, but are not limited to, phosphates and polyphosphates, polyaminopropane sulfonic acid (AMPS), sulfonated polyolefins, polyolefin polyolefins, azacycloalkane-2 , 2-diphosphonate (eg, azacycloheptane-2,2-diphosphonic acid), N-methylazacyclopentane-2,3-diphosphonic acid, ethane-1-hydroxy-1,1-diphosphonic acid (EHDP), and Diphosphonates such as ethane-1-amino-1,1-diphosphonate, and phosphonoalkane carboxylic acid are included. Useful inorganic and polyphosphates include monobasic, dibasic, and tribasic sodium phosphate, tetrasodium pyrophosphate (TSPP), pyrophosphate Tetrapotassium, sodium tripolyphosphate, tetrapolyphosphate, sodium trimetaphosphate, sodium hexametaphosphate, and mixtures thereof are included. Other useful tartar control agents include polycarboxylic acid polymers and polyvinyl methyl ether / maleic anhydride (PVM / MA) copolymers such as GANTREZ®. In some embodiments, the anticalculus agent is at least one of tetrasodium pyrophosphate and tetrapotassium pyrophosphate. In some embodiments, the anticalculus agent is 0.2% to 0.8%, 0.3% to 0.7%, 0.4% to 0.4% by weight based on the total weight of the composition. It is present in the composition in an amount of 0.6 wt%, or about 0.5 wt%.

  In any embodiment of each of the foregoing aspects, the oral care composition comprises a dentifrice, toothpaste, gel, toothpaste, mouthwash, mouthrinse, troche, tablet, spray, gum, or It may be a film. In certain embodiments, the oral care composition is a toothpaste, gel, or toothpaste.

  The oral care composition may further comprise additional components. Such additional ingredients include, but are not limited to, diluents, bicarbonates, pH adjusters, surfactants, foam modulators, thickeners, wetting agents, sweeteners, flavoring agents, pigments, Additional antibacterial agents, anti-cariogenic agents, and mixtures thereof may be included.

  In some embodiments, the oral care composition includes at least one bicarbonate that is useful for imparting a “clean feel” to teeth and gums, for example, by foaming and releasing carbon dioxide. Any orally acceptable bicarbonate can be used and includes, without limitation, alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate, ammonium bicarbonate and the like. Any orally acceptable bicarbonate can be used. The one or more additional bicarbonates are optionally present in a total amount of about 0.1% to about 50%, such as about 1% to 20% by weight, based on the total weight of the composition.

  In some embodiments, the oral care composition includes at least one pH adjuster. Such agents include acidifying agents to lower the pH, basifying agents to raise the pH, and buffers that control the pH within the desired range. For example, to provide a pH of 2-10, or in various exemplary embodiments, 2-8, 3-9, 4-8, 5-7, 6-10, 7-9, etc. One or more compounds selected from basifying agents and buffering agents can be included. Any orally acceptable pH adjuster can be used, without limitation, carboxylic acid, phosphoric acid, sulfuric acid, acid salts (eg monosodium citrate, disodium citrate, monosodium malate, etc.), hydroxylated Alkali metal hydroxide such as sodium, carbonate such as sodium carbonate, bicarbonate, sesquicarbonate, borate, silicate, phosphate (eg monosodium phosphate, trisodium phosphate), imidazole And the like. One or more pH adjusting agents are optionally present in an effective amount as a total to keep the composition in an orally acceptable pH range.

  The oral care composition may also include at least one surfactant. Any orally acceptable surfactant can be used, most of which are anionic, neutral, or amphoteric. Suitable anionic surfactants include, without limitation, water-soluble salts of C8-20 alkyl sulfates, sulfonated monoglycerides of C8-20 fatty acids, sarcosinates, taurates and the like. Illustrative examples of these and other classes include sodium lauryl sulfate, sodium coconut monoglyceride sulfonate, sodium lauroyl sarcosinate, sodium laurois lauriate laurate lauriate. , Sodium laurethcarboxylate, and sodium dodecylbenzenesulfonate. Suitable nonionic surfactants include, without limitation, poloxamers, polyoxyethylene sorbitan esters, aliphatic alcohol ethoxylates, alkylphenol ethoxylates, tertiary amine oxides, tertiary phosphine oxides. oxide), dialkyl sulfoxides and the like. Suitable amphoteric surfactants include, without limitation, derivatives of C8-20 aliphatic secondary and tertiary amines having an anionic group such as carboxylate, sulfate, sulfonate, phosphate or phosphonate. Betaine may also be used, a suitable example of which is cocoamidopropyl betaine. One or more surfactants are present in a total amount of about 0.01% to about 10%, such as about 0.05% to about 5%, or about 0.1% by total weight of the composition. % To about 2% by weight, optionally present.

  The oral care composition may include at least one foam control agent that is useful, for example, to increase the amount, thickness, or stability of the foam produced by the composition upon stirring. Any orally acceptable foam control agent can be used and includes, without limitation, polyethylene glycol (PEG), also known as polyoxyethylene. High molecular weight PEGs are suitable, including those having an average molecular weight of 200,000 to 7,000,000, such as 500,000 to 5,000,000 or 1,000,000 to 2,500,000. The one or more PEGs are in a total amount of from about 0.1% to about 10%, such as from about 0.2% to about 5%, or from about 0.25% to about 0.25% by weight, based on the total weight of the composition. 2% by weight, optionally present.

  The oral care composition may include, for example, at least one thickening agent useful for imparting a desired consistency and / or mouth feel to the composition. Any orally acceptable thickener can be used, without limitation, as a carbomer, also known as a carboxyvinyl polymer, and Irish moss and more specifically ι-carrageenan (iota-carrageenan) Also known carrageenans, cellulose polymers such as hydroxyethylcellulose, carboxymethylcellulose (CMC) and their salts. These salts include, for example, CMC sodium, natural gums such as Karaya, xanthan, gum arabic, and tragacanth, colloidal magnesium aluminum silicate, colloidal silica, and the like. Preferred types of thickening or gelling agents include homopolymers of acrylic acid crosslinked with alkyl ethers of pentaerythritol or alkyl ethers of sucrose, or carbomers. Carbomers are available as B. carbopol (R) series B.C. F. Commercially available from Goodrich. Particularly preferred Carbopols include Carbopol 934, 940, 941, 956, 974P and mixtures thereof. Silica thickeners such as DT267 (from PPG Industries) may also be used. One or more thickening agents are present in a total amount of about 0.01% to 15%, such as about 0.1% to about 10%, or about 0.2% by weight per total weight of the composition. % To about 5% by weight, optionally present.

  The composition may also include at least one viscosity modifier useful, for example, to contribute to inhibiting sedimentation or separation of the components, or to promote redispersibility when the liquid composition is agitated. Any orally acceptable viscosity modifier can be used and includes, without limitation, mineral oil, petrolatum, clay and organic modified clay, silica, and the like. The one or more viscosity modifiers are optionally present in a total amount of about 0.01% to about 10%, such as about 0.1% to about 5% by weight, based on the total weight of the composition. .

  The composition may also include at least one wetting agent. Any orally acceptable wetting agent can be used, such as, without limitation, glycerin, sorbitol (optionally as a 70 wt% solution in water), xylitol or low molecular weight polyethylene glycol (PEG). Polyhydric alcohol is included. Most humectants also function as sweeteners. One or more wetting agents are present in a total amount of from about 1% to about 70%, such as from about 1% to about 50%, from about 2% to about 25% by weight, based on the total weight of the composition; Or about 5% to about 15% by weight, optionally present.

  The oral care composition may include at least one sweetener useful, for example, to enhance the taste of the composition. The one or more sweeteners are highly dependent on the particular sweetener selected, but are typically 0.005% to 5% by weight, optionally 0, based on the total weight of the composition. 0.005% to 0.2% by weight, and optionally optionally 0.05% to 0.1% by weight per total weight of the composition.

  The composition may also include, for example, at least one flavoring agent useful for enhancing the taste of the composition. Any orally acceptable natural or synthetic flavor can be used, without limitation, tea flavor, vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, winter green oil (methyl salicylate), peppermint Essences including those derived from oil, clove oil, bay oil, anise oil, eucalyptus oil, citrus oil and fruit oil, lemon, orange, lime, grapefruit, apricot, banana, grape, apple, strawberry, cherry, pineapple, etc. , Coffee, cocoa, cola, peanut, almond and other beans and nut-derived flavors, adsorbent and encapsulated flavors, and the like. Similarly, the ingredients contained in the flavoring agent herein are ingredients that impart fragrance and / or other sensory effects in the oral cavity and include cooling or warming effects. Such ingredients include menthol, menthyl acetate, menthyl lactate, camphor, eucalyptus oil, eucalyptol, anethole, eugenol, cassia, oxanone, α-irisone, propenyl guaiethol, thymol, linalool, benzaldehyde. Cinnamaldehyde, N-ethyl-p-menthan-3-carboxamine, N, 2,3-trimethyl-2-isopropylbutanamide, 3- (1-menthoxy ) -Propane-1,2-diol, cinnamaldehyde glycerol acetal (CGA), menthone glycerol acetal (MGA) and the like. The one or more flavoring agents are present in a total amount of about 0.01% to about 5%, such as about 0.03% to about 2.5%, optionally about about per total weight of the composition. 0.05% to about 1.5% by weight, and optionally about 0.1% to about 0.3% by weight, optionally present.

  The composition may contain at least one colorant. Colorants herein include agents that impart specific gloss or reflectivity, such as pigments, dyes, lakes, and pearl foils. Any orally acceptable colorant can be used, without limitation, talc, mica, magnesium carbonate, magnesium silicate, magnesium aluminum silicate, titanium dioxide, red, yellow, brown, and black Iron oxide, ferric ammonium ferrocyanide, manganese violet, ultramarine, titanated mica, bismuth oxychloride, and the like. The one or more colorants are about 0.001% to about 20% by weight, eg, about 0.01% to about 10%, or about 0.1% by weight per total weight of the composition. % To about 5% by weight, optionally present.

  The composition may also include additional antimicrobial or preservatives such as chlorhexidine, triclosan, quaternary ammonium compounds (eg, benzalkonium chloride), or parabens such as methylparaben or propylparaben. The one or more additional antimicrobial or preservatives are about 0.01 wt.% To about 0.5 wt.%, Optionally about 0.05 wt.% To about 0.1 wt. % By weight, optionally present in the composition.

  The oral care composition may also include a fluoride ion source. Sources of fluoride ions include, but are not limited to, tin fluoride, sodium fluoride, potassium fluoride, potassium monofluorophosphate, sodium monofluorophosphate, ammonium monofluorophosphate, sodium fluorosilicate, fluorosilicate Ammonium, Olafrule (N′-octadecyltrimethylenediamine-N, N, N′-tris (2-ethanol) -dihydrofluoride) (N′-octadecyltrimethyldiamine-N, N, N′-tris (2-ethanol) -Fluoride), ammonium fluoride, and combinations thereof. In certain embodiments, the fluoride ion source includes tin fluoride, sodium fluoride, amine fluoride, sodium monofluorophosphate, and mixtures thereof. In certain embodiments, the oral care composition is in an amount sufficient to provide about 50 to about 5000 ppm fluoride ions, such as about 100 to about 1000, about 200 to about 500, or about 250 ppm fluoride ions. A fluoride ion source or a fluorine supply component may also be included. The fluoride ion source is about 0.001% to about 10% by weight, such as about 0.003% to about 5%, 0.01% to about 1%, or about 0.05% by weight. May be added to the composition at a level. However, it is clear that the weight of the fluoride salt that provides the appropriate level of fluoride ion will vary with the weight of the counter ion contained in the salt, and those skilled in the art can easily determine such amount. It is thought that. A preferred fluoride salt may be sodium fluoride.

  The composition may include, for example, a saliva stimulant useful in improving dry mice. Any orally acceptable saliva stimulant can be used and, without limitation, food acids such as citric acid, lactic acid, malic acid, succinic acid, ascorbic acid, adipic acid, fumaric acid and tartaric acid As well as mixtures thereof. One or more saliva stimulants are optionally present in a total amount effective for saliva stimulation.

  The composition may be an antisensitivity agent such as, for example, potassium salts such as potassium nitrate, potassium bicarbonate, potassium chloride, potassium citrate and potassium oxalate, capsaicin, eugenol, strontium salts, chloride salts and combinations thereof. May be included. Such agents may be added in an effective amount, for example, from about 1% to about 20% by weight based on the total weight of the composition, based on the agent selected.

  The composition may further comprise an antioxidant. Any orally acceptable antioxidant can be used, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin A, carotenoids, vitamin E, flavonoids, polyphenols, ascorbic acid, herbal antioxidants ( herbal antioxidant), chlorophyll, melatonin, and mixtures thereof.

  Experiments were performed to evaluate the biofilm reduction efficacy of compositions containing various concentrations of serine. Formulations containing either silica or natural calcium carbonate (NCC) as abrasives were tested.

The experimental procedure used in all of the examples below is the Biofilm Growth Inhibition of Manchester Model. The protocol for this model is as follows.
(1) Plaque was collected from four healthy volunteers and stored together as an inoculum. The absorbance (Optical Density) of the inoculum was 0.3 at 610 nm.
(2) Sterile hydroxyapatite (HAP) discs under anaerobic conditions with 1 mL of sterile artificial saliva (containing 0.01 wt% sucrose) and 1 mL of stored saliva in a 24-well microplate at 37 ° C. Incubated for hours.
(3) For each test dentifrice (and for each control), a treatment solution of 1 part dentifrice: 2 parts sterile distilled water was prepared by weight. Each freshly prepared treatment solution was added to 3 wells and the HAP disc was contacted there for 10 minutes.
(4) The liquid layer of each well was removed and replaced with 2 mL of sterilized artificial saliva.
(5) The disc was kept at 37 ° C. under anaerobic conditions for 8 days.
(6) At 2, 4, and 8 day intervals, discs were aseptically collected and transferred to thioglycolic acid medium (4.5 ml per disc) that had been reduced in half in advance.
(7) 100 μL diluted 10-4, 10-5, and 10-6 were plated in duplicate for each disc on neomycin / vancomycin (NV) agar for all gram negative anaerobes.
(8) Using a sterile spreader, the plate surface was stretched and incubated anaerobically at 37 ° C. for 72 hours, and then the number of colonies on each plate was counted.

  Log10 CFU / ml (CFU is colony forming unit) of each test dentifrice or control was calculated. A lower Log10 CFU / ml indicates that the tested dentifrice has a stronger potency in inhibiting biofilm growth.

  The test results are shown in Examples 1 to 3 below.

Example 1
In the first biofilm reduction test, the formulations listed in Table 1 were evaluated for their ability to reduce biofilm growth. The results obtained using the Biofilm Growth Inhibition of Manufacturer Model methodology (above) are shown in Table 1 along with the average log 10 CFU / ml obtained on the disk incubated for 8 days in method step 6.

  The results in Table 1 showed that the biofilm reduction efficacy of the formulation containing serine was improved regardless of the type of abrasive used (silica or natural calcium carbonate). There was no significant difference in potency between formulations containing 0.25 wt% serine and 0.75 wt% serine.

Example 2
To determine if there is an optimal serine concentration at which biofilm reduction efficacy is maximized, a second biofilm reduction test was performed using the dentifrice formulation described in Table 2 below. All test dentifrices contain 1% by weight zinc oxide and 0.5% by weight zinc citrate (Zn citrate). In the following results, formulations that share the same letter in “statistical significance” show no significant difference in their biofilm reduction efficacy.

  As can be seen from Table 2 above, 0.15 wt% serine of the silica-containing formulation exceeded all other tested formulations, as shown by the significantly reduced average Log10 CFU / ml value. This was followed by 0.15 wt.% Serine of the NCC containing formulation, followed by 0.25 wt.% Serine of the silica or NCC containing formulation, followed by 0.075 wt.% Serine of the silica or NCC containing formulation. As shown in Example 1, the formulation containing serine showed improved efficacy in biofilm reduction compared to the formulation without serine. The results obtained in this example also show that the biofilm reduction efficacy of the formulations was independent of whether they included silica or NCC as an abrasive.

Example 3
The test of Example 2 was performed again. In the following results, formulations that share the same letter in “statistical significance” show no significant difference in their biofilm reduction efficacy.

  As indicated above, the results obtained in Example 3 were similar to those obtained in Example 2. From the results of Examples 2 and 3, the biofilm reduction ability of the test sample increases as the serine concentration increases from 0 wt% to 0.15 wt%, and at higher serine concentrations (eg, 0.25 wt%). Although reduced, it can be seen that the capacity is still higher than zinc alone. A formulation containing 0.15% by weight serine has a higher capacity for its biofilm reduction efficacy compared to formulations containing higher or lower concentrations of serine in both silica-based and NCC-based formulations. Indicated.

Claims (23)

a. serine,
b. zinc oxide and zinc citrate in which zinc oxide to zinc citrate is in a weight ratio of 1.5: 1 to 4.5: 1;
An oral care composition comprising:   The weight ratio of zinc oxide to zinc citrate is 1.5: 1 to 4: 1, 1.7: 1 to 2.3: 1, 1.9: 1 to 2.1: 1, or about 2: The oral care composition of claim 1, which is 1.   The composition comprises serine in an amount of 0.05 wt% to 0.8 wt%, optionally 0.05 wt% to 0.39 wt%, 0.075 based on the total weight of the composition. The oral care composition according to any of the preceding claims, wherein the composition is from wt% to 0.25%, from 0.12 wt% to 0.25 wt%, or from 0.14 wt% to 0.2 wt%.   The oral care composition according to any of the preceding claims, wherein the composition comprises serine in an amount of about 0.15% by weight, based on the total weight of the composition.   The oral care composition according to any of the preceding claims, wherein the total concentration of zinc oxide and zinc citrate in the composition is from 0.2 wt% to 5 wt%, based on the total weight of the composition.   The composition comprises zinc oxide in an amount of 0.5 wt% to 1.5 wt%, and zinc citrate in an amount of 0.25 wt% to 0.75 wt%, based on the total weight of the composition. An oral care composition according to any of the preceding claims comprising.   The oral cavity according to any preceding claim, wherein the composition comprises zinc oxide in an amount of about 1 wt% and zinc citrate in an amount of about 0.5 wt%, based on the total weight of the composition. Care composition. a. serine,
b. one or more zinc salts,
An oral care composition included for use in reducing or inhibiting biofilm formation in the oral cavity.   The oral care composition of claim 8, wherein serine is present in the composition in an amount of 0.05 wt% to 0.8 wt% based on the total weight of the composition.   The oral care composition of claim 9, wherein serine is present in the composition in an amount of 0.05 wt% to 0.39 wt% based on the total weight of the composition.   The oral care composition of claim 10, wherein the composition comprises serine in an amount of 0.075 wt% to 0.25 wt% based on the total weight of the composition.   The oral care composition of claim 11, wherein the composition comprises serine in an amount of 0.12 wt% to 0.25 wt% based on the total weight of the composition.   The oral care composition according to claim 12, wherein the composition comprises serine in an amount of 0.14 wt% to 0.20 wt%, based on the total weight of the composition.   The oral care composition of claim 13, wherein the composition comprises serine in an amount of about 0.15% by weight, based on the total weight of the composition.   The oral care composition according to any one of claims 8 to 14, wherein the molar ratio of serine: total zinc salt is 0.01: 1 to 3: 1.   The oral care composition according to any one of claims 8 to 15, wherein the total concentration of zinc salt of the composition is 0.2 wt% to 5 wt% based on the total weight of the composition.   The oral care composition according to any one of claims 8 to 16, wherein at least one of the one or more zinc salts is zinc oxide.   The oral care composition according to any one of claims 8 to 17, wherein at least one of the one or more zinc salts is zinc citrate.   The composition comprises zinc oxide in an amount of 0.5 wt% to 1.5 wt%, and zinc citrate in an amount of 0.25 wt% to 0.75 wt%, based on the total weight of the composition. The oral care composition of claim 18.   20. An oral care composition according to claim 19, wherein the composition comprises zinc oxide in an amount of about 1% by weight, and zinc citrate in an amount of about 0.5% by weight, based on the total weight of the composition.   The weight ratio of zinc oxide to zinc citrate is 1.5: 1 to 4.5: 1, optionally 1.5: 1 to 4: 1, 1.7: 1 to 2.3: 1, 1.9. The oral care composition of claim 18, wherein the oral care composition is: 1 to 2.1: 1, or about 2: 1.   A method for reducing or inhibiting biofilm formation in the oral cavity, the method comprising contacting the oral cavity with an oral care composition according to any one of claims 1 to 21.   Use of a combination of (a) serine and (b) one or more zinc salts in an oral care composition for reducing or inhibiting biofilm formation in the oral cavity.